Cloning of hot and cold thermal receptors has advanced the understanding of the molecular basis of thermal sensation. Two (2) important remaining questions to be addressed are the identification of additional thermal receptor genes and the elucidation of the mechanism(s) that enable the receptor proteins to alter gating properties in response to changes in temperature. Existing technologies for studying thermal responses employ devices that elicit temperature changes, some under feedback control, at rates less than 4o C/sec. These rates are probably inadequate for characterizing distinct temperature responses of individual sensory neurons and for elucidating kinetic components of conformational changes in response to temperature. In phase 1 we demonstrated that our system for rapid temperature stimulation was viable. The goal of this project (phase 2) is to engineer, and bring to market, our device that can generate much faster temperature changes, under feedback control, than are currently attainable in the industry. This device will use a proprietary technology that enables rapid temperature switching of solutions applied from a focal application device built with nanofabricated components. The output of the device will be applied to excised membrane patches under patch clamp, or to individual cells voltage-clamped by discontinuous single-electrode voltage clamp or patch clamp. We intend to set an industry standard by employing nanofabrication techniques to allow our system to approach the theoretical limits of performance. Only a high performance system will enable the accurate deduction of the mechanism of action in thermally sensitive ion channels. An understanding of these mechanisms will lead to the creation of new and/or better pain therapeutics. We see a broad market in the pharmaceutical industry based on drug discovery and in academia based on pure science. Other applications of this device may also be possible.